The goal of this research is to invent, design, study and test effective voltammetric biosensors suitable for use in clinical therapeutic monitoring. The principal strategy will continue to be the preferential accumulation of the analyte onto the working electrode surface, followed by voltammetric quantitation of the surface-bound species. Analyte preconcentration will be accomplished by selective attachment, via covalent or ion- exchange reactions at modified electrodes, or preferential adsorption at ordinary electrodes. Polymeric coatings, with controllable permeability, will be evaluated for improving the selectivity and stability of the sensors. Sensing schemes for a variety of clinically-significant analytes, particularly therapeutic drugs, will be investigated. The features that distinguish the proposed sensors are inherent sensitivity (combination of a preconcentration step and advanced voltammetric techniques), selectivity (based on defined chemical reactions and discriminative properties of polymeric coatings), simplicity, economy, speed, and miniaturization. The investigation will cover both the fundamental and practical aspects of such biosensors, including detailed studies of the sensor behavior, systematic optimization of operational conditions, and competition and clinical tests of the resulting schemes. Specific issues to be addressed include highly sensitive adsorptive stripping measurement schemes for anticancer drugs and trace elements, appropriate tailoring (modification) of electrodes for effective use as preconcentrating surfaces, interferences due to endogeneous biological materials, coadministrated drugs, or principal metabolites, new modified electrodes based on composite and bilayer polymer assemblies and mixed carbon paste, effects of surface conditions and electrode treatment procedures on the adsorptive stripping response, and reproducible regeneration of a fresh sensor surface. By properly addressing the above issues significant analytical advantages will be achieved, and the utility of voltammetric biosensors as practical clinical tools will come much closer to realization.